1. Technical Field
The present invention relates in general, to a storage medium for isolated donor corneas and, in particular, to a corneal storage medium which extends the period of time surgical-quality corneas may be stored.
2. Background Information
Penetrating kertoplasty for the restoration of sight in patients with corneal opacity is highly successful. However, the short supply of surgical-quality donor corneas means that many patients wait up to a year for available donor tissue.
The quantity of surgical-quality donor corneas is determined by a combination of two factors: (1) the length of time between the death of the donor and the preservation of the cornea, and (2) the length of time that the tissue remains stored. Presently, procurement of a donor cornea no more than twelve hours after death and storage for no more than 72 hours constitute the guidelines for the distribution of donor tissues for transplant. Donor corneas with a preservation time of up to 96 hours are used on an emergency basis. Statistics indicate that if the upper limit of death-to-preservation time were to be extended from 12 hours to 24 hours, 50% more donor corneas would be available for transplant.
Development of methods for extending the time donor corneas may be stored has significant clinical as well as marketing implications. Extending corneal preservation time increases the quantity of tissues available for transplant, provides surgeons flexibility in performing operations, improves scheduling of elective surgery, and affords more cost efficient use of operating rooms. Patients benefit from the enhanced physiological quality of corneal tissues.
The importance of corneal preservation for transplantation has been recognized for over 70 years. Early attempts involved the use of hemolyzed serum. Other methods that have been evaluated include cryo-preservation and storage in a moist chamber, in autologous serum and in tissue culture medium. The applicability an organ culture system involving repeated medium changes has also been examined.
Of the above-described storage systems, maintenance of isolated corneas in tissue culture medium is the method most widely used. Specifically, Medium 199 with 5% dextran (McCarey-Kaufman medium) is credited with offering superior preservation of corneal endothelium. Corneas maintained in McCarey-Kaufman medium are kept clear and this by the inclusion in the culture medium of dextran. The thus stored corneas, however, tend to swell extensively when placed in an aqueous or salt solution after storage. Recently, the possible substitution of dextran with chondroitin sulfate was evaluated. While beneficial effects of chondroitin sulfate for long-term corneal storage remain to be documented, it has been reported that corneas stored in the presence of chondroitin sulfate swell and become slightly hazy.
Currently, donor corneas are stored refrigerated in McCarey-Kaufman medium in tightly sealed vials. Under these preservation conditions, the metabolic activity of the cornea is reduced and, therefore, the energy output may be inadequate for the tissue to maintain its transparency and minimal biological activity. In addition, since the storage vials are tightly capped, the limited amount of oxygen in the medium gradually decreases. As the oxygen content decreases, anaerobic glycolytic activity increases resulting in an accumulation of excess lactate in the storage medium. The lactic acid concentration in the storage medium of surgical-quality corneas in about 0.50 mM and about 2.0 mM or more for donor corneas not suitable for surgery. The formation of lactate is accompanied by the formation of an equimolar concentration of H+. A resulting reduction in intracellular pH would adversely affect the corneal tissue.